Impact of focal segmental glomerulosclerosis over the past decade.

OBJECTIVE: This is a study on the demographics and clinical outcomes including the response to therapy of patients with focal segmental glomerulosclerosis (FSGS) over the past decade. MATERIALS AND METHODS: All histologically proven FSGS cases diagnosed between 2008 and 2018 were analyzed for their clinical, laboratory, and histological characteristics including treatment that could influence the disease progression and renal outcome of these patients. We used the Columbia Classification for FSGS for the renal biopsy. RESULTS: There were two subgroups of FSGS patients; those with nephrotic syndrome and those without nephrotic syndrome. Patients with FSGS with non-nephrotic syndrome had poorer survival rates compared to the nephrotic group. For those without nephrotic syndrome, the indices responsible for progression involved more tubular and blood vessel lesions in addition to glomerular pathology compared to those with nephrotic syndrome. Patients with FSGS with nephrotic syndrome responded to immunosuppressants more favorably compared to the non-nephrotic group, though both groups responded with decreasing proteinuria. The nephrotic group had a better 10-year long-term survival rate of 92 vs. 72% for the non-nephrotic group (log-rank 0.002). The 10-year survival for the whole group of FSGS patients was 64%. CONCLUSION: Our data suggest that in FSGS, one of the significant components of the disease is the vascular and tubular damage, apart from the underlying glomerular pathology, resulting in varying responses to therapy, and the difference is reflected in inherently poorer response to immunosuppressant therapy in those without nephrotic syndrome as opposed to those with nephrotic syndrome, who responded to immunosuppressant therapy (IST) with stabilization of renal function and had less blood vessel and tubular lesions.

Evolution of IgA nephropathy in Singapore over four decades and a comparison of two cohorts from the first and fourth decade.

OBJECTIVE: In this study, we trace the changes in the clinical and histological pattern of IgA nephritis (IgAN) in Singapore as it has evolved over 4 decades and compare the clinical, demographic, histological, and renal outcome of patients with IgAN from the 1st decade and the 4th decade. MATERIALS AND METHODS: This is a retrospective study of all histologically proven IgAN diagnosed between 1976 and 2018. Clinical, laboratory, and histological characteristics between the 1st and the 4th decade, including treatment which could influence the disease progression and renal outcome of these two groups, were compared. We used the Oxford classification to compare the renal biopsy changes for these 2 decades as we were able to retrieve 125 renal biopsy tissues for the 1st cohort of IgAN studied in the 1970s for the comparative study. RESULTS: The commonest clinical presentation throughout the first 3 decades was asymptomatic hematuria and proteinuria (63, 52, and 49%, respectively). In the 4th decade, nephrotic syndrome (31%) was the commonest followed by asymptomatic hematuria and proteinuria (30%), hypertension (21%), and chronic renal failure (11%). The data showed that treatment can modify the Oxford MEST - Crescent scores. Renin-angiotensin system (RAS) blockers modified the S scores, immunosuppressants modified the T and C scores, and combination therapy with RAS blockers and immunosuppressants modified the E, S, and T scores. CONCLUSION: The Oxford MEST classification offers a robust and expressive classification for early and late disease progression with respect to the development of end-stage renal disease (ESRD). E and S seem to be indices of continuing disease activity with progressive glomerulosclerosis, probably still amenable to therapy, but T was a predictive indicator for those destined for ESRD and no longer amenable to therapy.

Severe infections in patients with lupus nephritis treated with immunosuppressants: A retrospective cohort study.

AIM: Lupus nephritis (LN) is associated with significant morbidity and mortality and hence usually treated aggressively with immunosuppressants. This predisposes LN patients to increased infections, yet few studies have evaluated LN patients for infective complications. We aimed to describe the epidemiology and identify risk factors for infections requiring hospitalization among patients with biopsy-proven LN. METHODS: This was a single-centre retrospective cohort study of patients with biopsy-proven LN between 1 January 2000 and 31 May 2009. Patients were excluded if they were <16 years old at time of biopsy, had previous kidney transplant or if pharmacotherapy data were incomplete. Hospitalizations for infections, bacteraemia and polymicrobial infections were recorded until patients' last visit or when they received immunosuppression for non-glomerulonephritis indications, such as solid organ transplant or chemotherapy. RESULTS: We studied 189 patients who had biopsy-proven lupus nephritis. Median age at diagnosis was 36.9 (IQR: 27.4, 47.5) years and 82% were female. Most patients received at least one immunosuppressant after LN diagnosis, including glucocorticosteroids in 94.2%. One hundred and four patients (60.3%) had at least one hospitalization for infection at 11 (1, 53) months from diagnosis. Bacteraemia occurred in 26 patients (13.8%) and 32 patients (16.9%) had polymicrobial infections. On multivariate analysis, LN relapse was associated with hospitalization for infection (OR 2.33 (1.18, 4.60), P = 0.01) and bacteraemia (OR 3.47 (1.05, 11.45), P = 0.04). Infection-related mortality occurred in 10 patients (5.3%). CONCLUSION: Serious infections are common among patients with LN and are associated with mortality.

30-year follow-up study of IgA nephritis in a Southeast Asian population: an evaluation of the Oxford histological classification
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BACKGROUND: In 1985 we reported that 11% of a cohort of 151 patients with IgA nephritis (IgAN) had developed end-stage renal disease (ESRD) after a follow-up period of 5 years. 15 years later, 35% had developed ESRD. METHODS: We retrieved 125 stored renal biopsy paraffin blocks of the original cohort. From these, 102 patients were included in the present study and scored according to the Oxford classification as 21 specimens with less than 8 glomeruli were excluded and in 2 others, tissue samples were too tiny for a re-block. ESRD was ascertained by linking the study cohort to the Singapore Renal Registry at the National Registry of Diseases Office. RESULTS: Renal survival curves for each of the Oxford MEST lesions: endocapillary proliferation (E) (p < 0.04), segmental glomerulosclerosis (S) (p < 0.05), tubular atrophy/interstitial fibrosis (p < 0.0001) were significantly associated with ESRD. Mesangial hypercellularity, less commonly associated with progressive chronic kidney disease (CKD) in the study, was independently associated with ESRD at 30 years (p < 0.03). In this cohort, E and S were associated with lower eGFR at presentation and doubling of serum creatinine in the first 5 years. This study's initial 5 years was representative of the "natural history" of IgAN since no renin-angiotensin system (RAS) blockers or immunosuppression were administered. This represents the early phase of disease progression. E and S may be considered "early disease activity predictors". CONCLUSION: Mesangial hypercellularity and tubular atrophy/interstitial fibrosis (M1 and T1/T2 lesion) of the Oxford classification independently predicted long term ESRD.
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Development and validation of a novel nomogram to predict diabetic kidney disease in patients with type 2 diabetic mellitus and proteinuric kidney disease.

PURPOSE: Differentiating between diabetic kidney disease (DKD) and non-diabetic kidney disease (NDKD) in patients with Type 2 diabetes mellitus (T2DM) is important due to implications on treatment and prognosis. Clinical methods to accurately distinguish DKD from NDKD are lacking. We aimed to develop and validate a novel nomogram to predict DKD in patients with T2DM and proteinuric kidney disease to guide decision for kidney biopsy. METHODS: A hundred and two patients with Type 2 Diabetes Mellitus (T2DM) who underwent kidney biopsy from 1st January 2007 to 31st December 2016 were analysed. Univariate and multivariate analyses were performed to identify predictive variables and construct a nomogram. The discriminative ability of the nomogram was assessed by calculating the area under the receiver operating characteristic curve (AUROC), while calibration was assessed using the Hosmer-Lemeshow goodness-of-fit test and calibration plot. Internal validation of the nomogram was assessed using bootstrap resampling. RESULTS: Duration of T2DM, HbA1c, absence of hematuria, presence of diabetic retinopathy and absence of positive systemic biomarkers were found to be independent predictors of DKD in multivariate analysis and were represented as a nomogram. The nomogram showed excellent discrimination, with a bootstrap-corrected C statistic of 0.886 (95% CI 0.815-0.956). Both the calibration curve and the Hosmer-Lemeshow goodness-of-fit test (p = 0.242) showed high degree of agreement between the prediction and actual outcome, with the bootstrap bias-corrected curve similarly indicating excellent calibration. CONCLUSIONS: A novel nomogram incorporating 5 clinical parameters is useful in predicting DKD in type 2 diabetes mellitus patients with proteinuric kidney disease.

Estimation of risk for major bleeding in native kidney biopsies in patients with multiple risk factors.

BACKGROUND AND AIMS: Individuals undergoing kidney biopsy are increasingly older and may have concurrent illnesses that cause deranged hematological and renal parameters that are associated with post-biopsy bleeding. We aimed to develop a clinical risk model to quantify bleeding risks in high-risk individuals with multiple risk factors. METHODS: Single-center retrospective cohort study of consecutive adults with serum creatinine ≥ 2 mg/dL (176 µmol/L) and had ultrasound-guided percutaneous native kidney biopsies between June 2011 and July 2015 in our tertiary referral center. The primary outcome was major bleeding, defined as need for red cell transfusion, radiological or surgical intervention, or if bleeding led to death within 7 days after kidney biopsy. RESULTS: Among 184 native kidney biopsies with serum creatinine ≥ 2 mg/dL, median age was 54.1 years and eGFR was 18.8 ml/min/1.73 m2. Major bleeding occurred in 19 biopsies (10.3%). Multivariate analysis accounting for age, weight, hemoglobin, platelet, prothrombin time and urea found that higher hemoglobin (adjusted OR 0.51, 95% CI 0.33-0.79, p = 0.003) and platelet (adjusted OR 0.99, 95% CI 0.98-0.99, p = 0.01) were independently associated with reduced major bleeding. A risk model that included (1) age ≥ 62 years old, (2) hemoglobin < 10 g/dL and (3) platelets ≤ 216 × 109/L as categorical variables predicted major bleeding post-biopsy. CONCLUSION: We developed a risk model that included multiple risk factors to quantify bleeding risks in native kidney biopsies with renal impairment.

A Descriptive Evaluation of Health Literacy and Determinants of COVID-19 Vaccine Acceptance among Patients with IgA Nephropathy with High Vaccine Uptake.

Aims: Shared decision-making regarding COVID-19 vaccination in IgA nephropathy involves the ability to handle health information regarding potential benefits and risk of flare, but few studies have evaluated health literacy in the context of vaccination. We aimed to evaluate the health literacy and COVID-19 vaccination uptake and acceptance in IgA nephropathy. Methods: Single-center cross-sectional study of 126 consecutive patients with IgA nephropathy. Health literacy was assessed using the HLS-EU-47 questionnaire. Determinants of vaccine acceptance such as contextual influences, individual and group influences, and vaccine-specific issues were adapted from the World Health Organization framework. Results: Forty-eight patients (38.1%) with IgAN nephropathy completed the survey between June and August 2021. The participants' median age was 40.5 (31.6, 52.8) years with median disease duration of 2.8 (1.3, 4.3) years. The median general health literacy index was 31.74 (29.88, 35.82) with significantly greater difficulty in the competency of appraising health information and in the domain of disease prevention (p < 0.001). Forty-five patients (93.8%) received at least one dose of COVID-19 vaccine between January and August 2021. Among the 3 unvaccinated patients, 2 intended to receive the vaccination while and 1 did not intend to get vaccinated. There was a high level of trust and belief that their government and healthcare providers had their best interests at heart and that the healthcare providers were honest about the vaccine's risk and benefits, although 31.2% did not understand how the vaccine works and 22.9% believed that there were other ways to prevent infection. Most thought there was adequate safety information, were confident in the system for tracking adverse events and had no issues with access to the vaccine. Conclusion: Participants with IgA nephropathy had high health literacy scores and low vaccine hesitancy. The determinants for vaccine acceptance can potentially guide efforts to optimize vaccination coverage.

Changes in metabolic parameters and adverse kidney and cardiovascular events during glomerulonephritis and renal vasculitis treatment in patients with and without diabetes mellitus.

BACKGROUND: Cardiovascular disease causes significant morbidity and mortality in patients with glomerulonephritis, which is increasingly diagnosed in older individuals who may have diabetes mellitus (DM). We evaluated the impact of DM on metabolic profile, renal and cardiovascular outcomes during treatment and follow-up of individuals with glomerulonephritis. METHODS: We performed a retrospective cohort study of 601 consecutive adults with biopsy-proven glomerulonephritis for factors associated with kidney failure, hospitalization for cardiovascular events, and death. Biopsies with isolated diabetic nephropathy were excluded. RESULTS: The median patient age was 49.8 years (36.7-60.9 years) with estimated glomerular filtration rate of 56.7 mL/min/1.73 m2 (27.7-93.2 mL/min/1.73 m2). DM was present in 25.4%. The most frequent diagnoses were minimal change disease (MCD) or focal segmental glomerulosclerosis (FSGS) (29.5%), lupus nephritis (21.3%), immunoglobulin A (IgA) nephropathy (19.1%), and membranous nephropathy (12.1%). The median follow-up was 38.8 months (interquartile range [IQR], 26.8-55.8 months). Among 511 individuals with lupus nephritis, anti-neutrophil cytoplasmic antibody-associated vasculitis, MCD/FSGS, membranous nephropathy, and IgA nephropathy, 52 (10.2%) developed kidney failure at a median 16.4 months (IQR, 2.3-32.2 months), while 29 (5.7%) had cardiovascular-related hospitalizations at 12.9 months (IQR, 4.8-31.8 months) and 31 (6.1%) died at 13.5 months (IQR, 2.5-42.9 months) after diagnosis. Cox regression analysis found that baseline DM was independently associated with kidney failure (adjusted hazard ratio [HR], 2.07; 95% confidence interval [CI], 1.06-4.05, p = 0.03) and cardiovascular-related hospitalization (adjusted HR, 2.69; 95% CI, 1.21-5.98, p = 0.02) but not with mortality. CONCLUSION: DM was strongly associated with kidney failure and hospitalization for cardiovascular events in patients with biopsy-proven glomerulonephritis.

Synergistic impact of pre-diabetes and immunosuppressants on the risk of diabetes mellitus during treatment of glomerulonephritis and renal vasculitis.

BACKGROUND: Glomerulonephritis is often treated with kidney-saving, but potentially diabetogenic immunosuppressants such as glucocorticosteroids and calcineurin inhibitors. Unfortunately, there are little data on dysglycemia before and after diagnosis and during treatment of glomerulonephritis. We aimed to evaluate the occurrence and risk factors for pre-diabetes and incident diabetes among non-diabetic patients with glomerular disease with or without treatment with immunosuppressants. METHODS: A single-center, retrospective cohort study was performed on 229 non-diabetic immunosuppressantnaïve adults diagnosed with glomerulonephritis and renal vasculitis. Patients with known diabetes and prior immunosuppressant treatment were excluded. Outcomes of new-onset pre-diabetes and new-onset diabetes were defined according to American Diabetic Association criteria. RESULTS: Pre-diabetes was present pre-biopsy in 74 of the 229 patients (32.3%). During the median follow-up of 34.0 (23.3-47.5) months, 29 patients (12.7%) developed new-onset diabetes and 58 (25.3%) had new-onset prediabetes. Immunosuppressive therapy in patients with pre-existing pre-diabetes was associated with increased odds of new-onset diabetes compared to those without either risk factor (26.0% versus 5.0%; odds ratio, 6.67; 95% confidence interval [CI], 1.41 to 31.64), P = 0.02). CONCLUSION: New-onset diabetes after immunosuppressant treatment occurred in one-quarter of patients with glomerulonephritis and pre-existing pre-diabetes. Physicians should screen for pre-diabetes when planning treatment with immunosuppressants, as its presence significantly increases the risk of diabetes mellitus.

Bleeding Complications and Adverse Events After Desmopressin Acetate for Percutaneous Renal Transplant Biopsy.

INTRODUCTION: Percutaneous renal biopsy remains critical for the workup of renal allograft dysfunction but is associated with the risk of bleeding. Prophylactic intravenous desmopressin has been proposed to reduce bleeding risk in native renal biopsies, but its efficacy in the renal transplant population is unclear and adverse events such as severe hyponatraemia have been reported. MATERIALS AND METHODS: We conducted a single-centre retrospective cohort study involving adult (≥21 years old) renal transplant recipients with impaired renal function (serum creatinine ≥150 µmol/L) who underwent ultrasound-guided renal allograft biopsies from 2011‒2015 to investigate the effect of prebiopsy desmopressin on the risk of bleeding and adverse events. RESULTS: Desmopressin was administered to 98 of 195 cases who had lower renal function, lower haemoglobin and more diuretic use. Postbiopsy bleeding was not significantly different between the 2 groups (adjusted odds ratio [OR] 0.79, 95% confidence interval [CI] 0.26‒2.43, P = 0.68) but desmopressin increased the risk of postbiopsy hyponatraemia (sodium [Na] <135 mmol/L) (adjusted OR 2.24, 95% CI 1.10‒4.59, P = 0.03). Seven cases of severe hyponatraemia (Na <125 mmol/L) developed in the desmopressin group, while none did in the non-desmopressin group. Amongst those who received desmopressin, risk of hyponatraemia was lower (OR 0.26, 95% CI 0.09‒0.72, P = 0.01) if fluid intake was <1 L on the day of biopsy. CONCLUSION: Prophylactic desmopressin for renal allograft biopsy may be associated with significant hyponatraemia but its effect on bleeding risk is unclear. Fluid restriction (where feasible) should be recommended when desmopressin is used during renal allograft biopsy. A randomised controlled trial is needed to clarify these outcomes.

Desmopressin for the prevention of bleeding in percutaneous kidney biopsy: efficacy and hyponatremia.

BACKGROUND: Desmopressin is used to reduce bleeding complications for kidney biopsies with azotemia but little is known about desmopressin-induced hyponatremia in these individuals. We aimed to evaluate the impact of desmopressin prophylaxis on severe hyponatremia and bleeding after kidney biopsies in individuals with renal impairment. METHOD: This is a single-center retrospective cohort study of consecutive adults with serum creatinine ≥ 150 µmol/L and had ultrasound-guided percutaneous native or transplant kidney biopsies between June 2011 and July 2015. Data were retrieved from electronic medical records. Primary outcomes were the use of desmopressin prophylaxis and severe hyponatremia (serum sodium ≤ 125 mmol/L) within 7 days post-biopsy. Secondary outcome was post-biopsy bleeding. RESULTS: 240 native kidney and 196 allograft biopsies were performed. Median age was 51 (IQR 42.3, 60) years and eGFR was 21.9 (12.9, 30.1) ml/min/1.73 m2. Although patients prescribed desmopressin prophylaxis (n = 226) had higher serum creatinine [279 (201, 392) vs. 187 (160, 241), p < 0.001], bleeding (15.0% vs. 13.3%, p = 0.60) was not significantly different with and without desmopressin. Severe hyponatremia occurred in 30 biopsies (6.9%) with nadir serum sodium level of 122 (119, 124) mmol/L at 3 (2, 5) days after biopsy, more frequently among those with desmopressin prophylaxis (10.7% vs. 3.0%, p = 0.002). Multi-variate analysis found that pre-biopsy serum sodium level [adjusted OR 0.80 (95% CI 0.72, 0.90), p < 0.001] and desmopressin prophylaxis [adjusted OR 4.02 (95% CI 1.58, 10.21), p = 0.003] were independently associated with severe hyponatremia after kidney biopsy. CONCLUSION: Pre-biopsy desmopressin was associated with severe hyponatremia in individuals with renal impairment; hence, susceptible patients given desmopressin should be closely monitored.

A Global Evolutionary Trend of the Frequency of Primary Glomerulonephritis over the Past Four Decades.

OBJECTIVE: The pattern of glomerulonephritis (GN) in Singapore is compared with that of 19 other countries to review changing trends in the evolution of GN in Asian, Eastern, and Western countries. METHOD: Three thousand two hundred and eighty-nine renal biopsies in Singapore were reviewed and compared with that of 19 other countries. RESULTS: IgA nephritis is on the decline in many countries, including Singapore, though it still remains the commonest GN in Singapore. Membranous GN that if used to be more frequently present in Western countries has also declined though it continues a rising trend in countries such as Singapore and China. Worldwide, the frequency of focal sclerosing glomerulosclerosis (FSGS) continues to increase in many countries, but in some countries, the frequency is still low with mesangiocapillary GN remaining indigenous. CONCLUSION: Urbanization and socioeconomic changes and less exposure to parasitic and other infestations have transformed Singapore's pattern, which is tending toward that of more developed countries. Antigenic exposure due to lifestyle changes, environmental, and industrial pollution are significant contributory factors that affect the evolutionary trend of GN in many countries. The rising trend in the frequency of FSGS may reflect aging and obesity.

National Health Survey on the prevalence of urinary abnormalities in the population: then and now (1975 to 2012).

INTRODUCTION: This paper presents the results of a community survey on urinary abnormalities which covered 1/80th of the population of Singapore in 1975. These findings were compared with the data from the Singapore National Service Registrants in 1974 as well as data from a recent survey in Singapore and that of other Asian and Western countries. MATERIALS AND METHODS: The study covered 18,000 persons aged 15 years and above, representing a sampling fraction of 1/80th of the population. A total of 16,808 respondents attended the field examination centres, of whom 16,497 had their urine sample tested representing 92.7% of the sample population. RESULTS: In the dipstick urine testing at the field examination centres, 769 subjects (4.6%) were found to have urinary abnormalities. Two hundred and eighty-two (36.7%) of these 769 subjects were found to have urinary abnormalities based on urine microscopy constituting a prevalence of 1.71%. The prevalence of proteinuria was 0.63% and for both haematuria and proteinuria was 0.73%. The prevalence for hypertension was 0.43% and renal insufficiency was 0.1%. DISCUSSION: The consensus is that routine screening for chronic kidney disease (CKD) in the general population is not cost effective as the yield is too low. Whilst, most studies showed that screening of the general population was not cost effective, it has been suggested that screening for targeted groups of subjects could help to identify certain risk groups who may benefit from early intervention to prevent or retard the progression of CKD. CONCLUSION: The prevalence of urinary abnormalities in Singapore has remained the same, now and three decades ago.